Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney
Yoshiharu Muto, Parker C. Wilson, Nicolas Ledru, Haojia Wu, Henrik Dimke, Sushrut S. Waikar, Benjamin D. Humphreys
Abstract
The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
Datasets
1. Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney - RNAseq
Metadata
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HANCESTRO:000517065 cells NCBITaxon:960619985 cells e7372715-150e-4117-a11b-a88ea56ce5c55464 cells d8b737fb-8a38-4a1d-a421-cbc81edddd054114 cells c47a5959-a0ed-4276-8a8d-5f136f1edd293804 cells 84824920-47bc-4929-b123-87574944aa373683 cells 8628f96c-2d97-4579-951c-044017ef6f0e2920 cells flash-freezing19985 cells UBERON:000122519985 cells 83133dd2-efc7-4f0a-8d8b-61cfcb9440955464 cells a0d05ece-11da-451c-8178-bc66d038afa64114 cells 3f282d42-57bd-4564-bae7-1515329032863804 cells 747d1ffc-3482-4ca5-8af9-54490ff3ba403683 cells 3f1a27d8-4be7-45c6-9f74-01732787f26d2920 cells 364545f5-d190-4f2f-bae9-20fb11f39b3e5464 cells cccd2996-0f80-4b49-b210-86a55b800dd14114 cells 82b6c04d-fea7-4ec2-8a75-7e32be7d55a63804 cells bbb332be-3eac-4a3f-ae93-c7851506ed703683 cells 89f2a9f6-25fc-4d0a-af0e-af393f20f7f12920 cells [kidney cancer]7487 cells [gastroesophageal reflux disease,diverticulitis,depressive disorder,kidney cancer,Lyme disease,anxiety disorder,arthritic joint disease]5464 cells [obstructive sleep apnea syndrome,kidney cancer,acoustic neuroma]4114 cells [pericardial effusion,essential hypertension,benign prostatic hyperplasia,kidney cancer,acute kidney tubular necrosis]2920 cells epithelial cell of proximal tubule5485 cells kidney loop of Henle thick ascending limb epithelial cell4435 cells kidney distal convoluted tubule epithelial cell3250 cells kidney connecting tubule epithelial cell1805 cells renal alpha-intercalated cell1107 cells renal principal cell1022 cells kidney capillary endothelial cell1008 cells parietal epithelial cell552 cells renal beta-intercalated cell349 cells cortex of kidney19985 cells Hispanic or Latin American2920 cells 61-year-old human stage5464 cells 54-year-old human stage4114 cells 52-year-old human stage3804 cells 50-year-old human stage3683 cells 62-year-old human stage2920 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/9b02383a-9358-4f0f-9795-a891ec523bcc
Alias names
GSE151302, PMID33850129, PMC8044133
Cite this study
Muto, Y., Wilson, P.C., Ledru, N., Wu, H., Dimke, H., Waikar, S.S. and Humphreys, B.D., 2021. Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney. Nature communications, 12(1), p.2190. https://doi.org/10.1038/s41467-021-22368-w
